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TALAL M. AL-QAOUD, DIXON B. KAUFMAN, PETER J. FRIEND, and JON S. ODORICO
CHAPTER 42
42.1 The transplant library on OvidSP
LISET H. M. PENGEL
42.2 The transplant library on Evidentia
LISET H. M. PENGEL
Preface to the First Edition
Renal transplantation is now an accepted treatment of patients in end-stage renal failure. A successful transplant restores not merely life but an acceptable quality of life to such patients. The number of patients in endstage renal failure in the Western World who might be treated by hemodialysis and transplantation is considerable and comprises some 30-50 new patients/million of population. Unfortunately in most, if not all, countries the supply of kidneys for transplantation is insufficient to meet the demand. Furthermore, hemodialysis facilities are usually inadequate to make up this deficit so that many patients are still dying of renal disease who could be restored to a useful and productive life. Nevertheless, few of us would have imagined even 10 years ago that transplantation of the kidney would have become such a relatively common procedure as is the case today, and indeed well over 30,000 kidney transplantations have been performed throughout the world.
Transplantation of the kidney for the treatment of renal failure has been an attractive concept for many years. As long ago as 1945, three young surgeons at the Peter Bent Brigham Hospital in Boston, Charles Hufnagel, Ernest Landsteiner and David Hume, joined the vessels of a cadaver kidney to the brachial vessels of a young woman who was comatose from acute renal failure due to septicemia. The kidney functioned for several days before it was removed, and the woman regained consciousness. Shortly afterwards, the woman’s own kidneys began to function and she made a full recovery. The advent of the artificial kidney at that time meant that this approach to the treatment of acute renal failure was no longer necessary, but attention was soon given to the possibility of transplanting kidneys to patients with end-stage renal failure who were requiring dialysis on the newly developed artificial kidney to stay alive.
Although the first experimental kidney transplants in animals were reported first in Vienna by Dr. Emerich Ulmann in 1902 and then in 1905 by Dr. Alexis Carrel in the United States, the problem of rejection was not mentioned by either author. Later in 1910, Carrel did discuss the possible differences between an autograft and a homograft. The vascular techniques developed by Carrel for the anastomosis of the renal vessels to the recipient vessels are still used today. But in 1923, Dr. Carl Williamson of the Mayo Clinic clearly defined the difference between an autografted and homografted kidney and even published histological pictures of a rejecting kidney. Furthermore, he predicted the future use of tissue matching in renal transplantation.
It is unfortunate that the lower animals, such as the dog, do not possess a blood grouping like that of man. In the future it may be possible to work out a satisfactory way of determining the reaction of the recipient’s blood serum or tissues to those of the donor and the reverse; perhaps in this way we can obtain more light on this as yet relatively dark side of biology.
The recognition that allogeneic tissues would be rejected was further established in later years by Drs. Gibson and Medawar, who treated burn patients with homografts in Glasgow during the Second World War. Indeed, it was the crash of a bomber behind the Medawars’ house in Oxford during the early years of the war that first stimulated his interest in transplantation, especially of skin.
In his address at the opening of the new Oxford Transplant Unit in 1977, Sir Peter Medawar recounted this event.
Early in the war, an R.A.F. Whitley bomber crashed into a house in North Oxford with much serious injury and loss of life. Among the injured was a young man with a third degree burn extending over about 60% of his body. People burned as severely as this never raised a medical problem before: they always died; but the blood transfusion services and the control of infection made possible by the topical use of sulphonamide drugs now made it possible for them to stay alive. Dr. John F. Barnes, a colleague of mine in Professor H. W. Florey’s School of Pathology, asked me to see this patient in the hope that being an experimental biologist I might have some ideas for treatment. With more than half his body surface quite raw, this poor young man was a deeply shocking sight; I thought of and tried out a number of ingenious methods, none of which worked, for ekeing out his own skin for grafting, trying to make one piece of skin do the work of ten or more. The obvious solution was to use skin grafts from a relative or voluntary donor, but this was not possible then and it is not possible now.
I believe I saw it as my metier to find out why it was not possible to graft skin from one human being to another, and what could be done about it. I accordingly began research on the subject with the Burns Unit of the Glasgow Royal Infirmary, and subsequently in the Zoology Department in Oxford. If anybody had then told me that one day, in Oxford, kidneys would be transplanted from one human being to another, not as a perilous surgical venture, but as something more in the common run of things, I should have dismissed it as science fiction; yet it is just this that has come about, thanks to the enterprise of Professor Morris and his colleagues.
Nevertheless in 1951, David Hume in Boston embarked on a series of cadaver kidney transplants in which the kidney was placed in the thigh of the recipient. All but one of these kidneys were rejected within a matter of days or weeks, the one exception being a patient in whom the kidney functioned for nearly 6 months and enabled the patient to leave the hospital! This event provided hope for the future as no immunosuppressive therapy had been used in this patient. At this time, the problems of rejection of kidney allografts in the dog were being clearly defined by Dr. Morton Simonsen in Copenhagen and Dr. William Dempster in London, but in 1953, a major boost to transplantation research was provided by the demonstration, by Drs. Rupert Billingham, Lesley Brent and Peter Medawar, that tolerance to an allogeneic skin graft in an adult animal could be produced by injecting the fetus with donor strain
tissue, thus confirming experimentally the clonal selection hypothesis of Burnet and Fenner in the recognition of self and non-self. The induction of specific unresponsiveness of a host to a tissue allograft has remained the ultimate goal of transplant immunologists ever since.
Then in 1954, the first kidney transplant between identical twins was carried out successfully at the Peter Bent Brigham Hospital which led to a number of further successful identical twin transplants in Boston and elsewhere in the world over the next few years.
There still remained the apparently almost insoluble problem of rejection of any kidney other than an identical-twin kidney. The first attempts to suppress the immune response to a kidney allograft employed total body irradiation of the recipient and were carried out by Dr. Merril’s group in Boston, two groups in Paris under the direction of Drs. Kuss and Hamburger, respectively, and by Professor Shackman’s group in London. Rejection of a graft could be suppressed by irradiation, but the complications of the irradiation were such that this was really an unacceptable approach, although an occasional relatively long-term acceptance of a graft provided encouragement for the future.
Then came the discovery by Drs. Schwartz and Dameshek in 1959 that 6-mercaptopurine could suppress the immune response of rabbits to human serum albumin. Shortly afterwards, they showed that the survival of skin allografts in rabbits was significantly prolonged by the same drug. This event ushered in the present era of renal transplantation, for very quickly Roy Calne in London and Charles Zukoski working with David Hume in Virginia showed that this same drug markedly prolonged the survival of kidney allografts in dogs. And indeed,6-mercaptopurine was first used in a patient in Boston in 1960. Elion and Hitchings of the Burroughs Wellcome Research Laboratories in New York State then developed azathioprine, which quickly replaced 6-mercaptopurine in clinical practice as it was less toxic. With the addition of steroids, the standard immunosuppressive therapy of today was introduced to the practice of renal transplantation in the early sixties.
Not that this meant the solution of the problems of renal transplantation for this combination of drugs was dangerous and mortality was high in those early years. But there was a significant number of long-term successful transplants, and as experience grew, the results
of renal transplantation improved. Another major area of endeavor in renal transplantation at that time was directed at the study of methods of matching donor and recipient for histocompatibility antigens with the aim of lessening the immune response to the graft and so perhaps allowing a decrease in the immunosuppressive drug therapy. Although this aim has only been achieved to any great extent in siblings who are HLA identical, tissue typing has made a significant contribution to renal transplantation, perhaps best illustrated by the recognition in the late sixties that the performance of a transplant in the presence of donor-specific presensitization in the recipient leads to hyperacute or accelerated rejection of the graft in most instances. Nevertheless, the more recent description of the Ia-like system in man (HLA-DR) may have an important impact on tissue typing in renal transplantation. The present decade also has seen an enormous effort directed at immunological monitoring in renal transplantation and at attempts to induce experimental specific immunosuppression. We have solved most of the technical problems of renal transplantation; we have been left with the problem of rejection and the complications arising from the drug therapy given to prevent rejection.
Although the contributions in this book cover all aspects of renal transplantation, certain subjects, as for example immunological monitoring before transplantation, transplantation in children and cancer after renal transplantation, have received considerable emphasis as they do represent developing areas of great interest, and I must take responsibility for this emphasis. For in the seventies we have seen many of the principles and practice of renal transplantation become established and the areas of future investigation become more clearly defined. With an ever-increasing demand for renal transplantation, more and more people in many different disciplines, doctors (surgeons, physicians, pathologists, virologists, immunologists), nurses, scientists and ancillary staff are becoming involved in renal transplantation either in the clinic or in the laboratory. It is to these people I hope this book will be of value.
Peter J. Morris Oxford, UK November 1978
Sir
Preface to the Eighth Edition
Kidney transplant patients and practitioners benefit from updated knowledge of current and improved practice guidelines and novel techniques, in addition to being familiar with well-established principles. For these reasons we have sought out leading international experts to write the chapters of this 8th edition of the Textbook of Kidney Transplantation. What has not changed over the past 41 years since the first edition is Professor Morris’s dedication to the textbook’s quality and his personal attention to the details that are included. He has been the lead editor since the first edition, indeed the sole editor of the first five editions. Professor Marson and Knechtle are delighted that he has chosen to include us as editors, as this text remains the most widely circulated authoritative book on the subject of kidney transplantation, used internationally to help develop practice guidelines and train specialists. We are furthermore grateful to the authors who have produced the content of this 8th edition, including its up-to-date outcomes data and analysis of the evidence supporting current practice in the field. Finally, we thank the leadership of Elsevier for its excellent communication with the authors and editors and for their technical assistance with all aspects of the production of this complex project.
In this 8th edition, we have chosen to combine the chapters on azathioprine and mycophenolate based on the relatedness of these compounds as inhibitors of cell proliferation. We have added two new chapters, one addressing kidney allocation because policy varies in the international community, reflecting the ethical and societal values of different countries and populations. Secondly, we have added a chapter on biomarkers of kidney injury and rejection. The latter is in recognition of the need for better monitoring tools for kidney injury and rejection to guide therapy and patient management. Given the large number of candidate assays for injury and rejection and their relatively nascent status with respect to clinical use, we suspect that this will be a rapidly developing field in coming years and will help guide improvement of long-term kidney transplant outcomes. The chapter in the previous edition on belatacept has merged with the chapter on antibody and fusion
proteins and includes considerable new data on the clinical use of costimulation blockade.
Some areas of renal transplantation remain challenges for the field and this certainly would include the sensitized patient, antibody-mediated rejection, and management of chronic allograft failure. These topics are addressed in detail in associated chapters. Quite a number of chapters have been completely rewritten by new authors compared with the 7th edition, and we believe that these new chapters offer refreshing perspectives on their respective topics. We acknowledge that our field continues to be guided by new basic and clinical research that in many cases is beyond the scope of this text, despite our desire to treat subjects comprehensively. We have sought to include what is most pertinent to current clinical practice in the field. Our hope is that the coming decades will continue to build on the remarkable record of progress in kidney transplantation that we have witnessed since the first successful kidney transplant in 1954 by the late Joseph Murray at Peter Bent Brigham Hospital in Boston. Ours is an exciting field that offers improved and extended life to many persons with severely impaired renal function. It is also our hope that improved immunosuppressive therapy will further prolong graft survival and reduce the side effects of infection and malignancy, ultimately extending patient survival yet further. Improved preservation techniques offer the prospect of increasing the use of kidneys that were previously considered to be of inadequate quality, and thereby increase the supply of donor kidneys. Improved antiviral agents have made possible the use of HIV-positive and hepatitis C-positive donor kidneys. These innovations are described in this updated text, which we expect will inspire further good work.
Stuart J. Knechtle Durham, NC, USA
Lorna P. Marson Edinburgh, UK
Sir Peter J. Morris Oxford, UK
Gaurav Agarwal, MD
Assistant Professor of Medicine University of Alabama at Birmingham Birmingham, Alabama, USA
Talal M. Al-Qaoud, MD, FRCSC Assistant Professor of Surgery Department of Surgery, Division of Transplantation University of Maryland Baltimore, Maryland, USA
Barbara D. Alexander, MD, MHS Department of Medicine, Division of Infectious Diseases Duke University Durham, North Carolina, USA
Richard D.M. Allen, MBBS, FRACS Professor Emeritus University of Sydney Sydney, Australia
Frederike Ambagtsheer, PhD, LL.M. Doctor
Internal Medicine, Transplantation and Nephrology Erasmus MC Rotterdam, Netherlands
Rolf N. Barth, MD Professor Department of Surgery University of Maryland School of Medicine Baltimore, Maryland, USA
Amit Basu, MD, FACS, FRCS Attending Surgeon Surgery Jamaica Hospital Medical Center Jamaica, New York, USA
Tomas Castro-Dopico, MBiochem, PhD Research Associate Molecular Immunity Unit, Department of Medicine University of Cambridge Cambridge, United Kingdom
Eileen T. Chambers, MD Associate Professor Pediatrics and Surgery Duke University Durham, North Carolina, USA
Contributors
Jeremy R. Chapman, AC, FRACP, FRCP Clinical Director Division of Medicine and Cancer Westmead Hospital, Westmead Sydney, New South Wales, Australia
Menna R. Clatworthy, BSc, MBBCh, PhD, FRCP NIHR Research Professor and Reader in Immunity and Inflammation
Molecular Immunity Unit, Department of Medicine University of Cambridge Cambridge, United Kingdom
Bradley Henry Collins, MD Associate Professor Department of Surgery Duke University Medical Center Durham, North Carolina, USA
Robert B. Colvin, MD Benjamin Castleman Distinguished Professor of Pathology Pathology
Harvard Medical School and Massachusetts General Hospital Boston, Massachusetts, USA
Lynn D. Cornell, MD Consultant, Division of Anatomic Pathology Associate Professor of Laboratory Medicine and Pathology Mayo Clinic Rochester, Minnesota, USA
Sylvia F. Costa, MD Adjunct Assistant Professor Medicine, Division of Infectious Diseases Duke University Durham, North Carolina, USA
Alice Crane, MD, PhD Doctor Urology Cleveland Clinic Cleveland, Ohio, USA
Andrew Davenport, MD, FRCP
Professor of Dialysis and ICU Nephrology
UCL Department for Nephrology
Royal Free Hospital University College London London, United Kingdom
Matthew J. Ellis, MD
Medical Director Kidney Transplant Nephrology
Duke University Durham, North Carolina, USA
Brian Ezekian, MD
General Surgery Resident Department of Surgery
Duke University Medical Center Durham, North Carolina, USA
Casey Victoria Farin, MD
Clinical Fellow
Multiple Sclerosis and Neuroimmunology Department of Neurology
Duke University Durham, North Carolina, USA
Alton B. Farris III, MD
Associate Professor, and Director Laboratory of Nephropathology and Electron Microscopy Department of Pathology
Emory University Atlanta, Georgia, USA
Jay A. Fishman, MD Professor of Medicine
Harvard Medical School; Physician
Division of Infectious Disease and Massachusetts General Hospital Transplant Center Boston, Massachusetts, USA
Sander Florman, MD Professor of Surgery, Director Recanati/Miller Transplantation Institute
Icahn School of Medicine at Mount Sinai New York City, New York, USA
John L.R. Forsythe, MD, FRCS Eng, FRCS Ed, FEBS, FRCPEd
Honorary Professor
Transplant Surgery
University of Edinburgh Edinburgh, United Kingdom
Peter J. Friend, MD
Professor of Transplantation
Nuffield Department of Surgical Sciences University of Oxford Oxford, United Kingdom
Susan V. Fuggle, DPhil, MSc, BSc
Professor of Transplant Immunology
Nuffield Department of Surgical Sciences University of Oxford; Consultant Clinical Scientist
Transplant Immunology and Immunogenetics Laboratory, Oxford Transplant Centre
Oxford University Hospitals NHS Foundation Trust Oxford, United Kingdom
Rouba Garro, MD Assistant Professor Pediatrics
Emory University Atlanta, Georgia, USA
Robert S. Gaston, MD Director
Comprehensive Transplant Institute; Professor of Medicine and Surgery
Robert G. Luke Endowed Chair in Transplant Nephrology University of Alabama at Birmingham Birmingham, Alabama, USA
Edward K. Geissler, PhD University Hospital Regensburg Department of Surgery Division of Experimental Surgery Regensburg, Germany
Sommer Elizabeth Gentry, PhD Professor Mathematics
United States Naval Academy Annapolis, Maryland, USA; Research Associate Surgery
Johns Hopkins University School of Medicine Baltimore, Maryland, USA
James A. Gilbert, BM, BS, MA(Ed), FRCS Consultant Transplant and Vascular Access Surgeon Renal and Transplant
Oxford University Hospitals Oxford, United Kingdom
Public Health Program Associate Department of Surgery, Division of Transplantation
Emory University School of Medicine Atlanta, Georgia, USA
Benson M. Hoffman, MA, PhD
Associate Professor Department of Psychiatry and Behavioral Sciences
Duke University Medical Center Durham, North Carolina, USA
Matthew L. Holzner, MD
Postdoctoral Fellow
Recanati/Miller Transplantation Institute
Icahn School of Medicine at Mount Sinai New York City, New York, USA
Joanna Hooten, BS, MD Staff Dermatologist Chelsea Dermatology Chelsea, Michigan, USA
James P. Hunter, BSc (Hons), MBChB, MD, FRCS
Senior Clinical Research Fellow and Consultant Transplant
Surgeon University Hospitals Coventry and Warwickshire Coventry, United Kingdom; University of Oxford Oxford, United Kingdom
Alan G. Jardine, BSc, MD, FRCP Professor of Renal Medicine and Head of the Undergraduate Medical School Institute of Cardiovascular and Medical Sciences University of Glasgow Glasgow, United Kingdom
Laura S. Johnson, MD
Assistant Professor Department of Surgery Georgetown University School of Medicine Washington, District of Columbia, USA
Arman A. Kahokehr, MB, PhD, FRACS Fellow in Reconstructive Urology Duke University Medical Center Durham, North Carolina, USA
Dixon B. Kaufman, MD, PhD
Ray D. Owen Professor of Surgery Department of Surgery, Division of Transplantation University of Wisconsin-Madison School of Medicine and Public Health Madison, Wisconsin, USA
Karen L. Keung, MBBS, FRACP Nephrologist
Centre for Transplant and Renal Research Westmead Institute of Medical Research Westmead, New South Wales, Australia
Allan D. Kirk, MD, PhD Professor and Chairman Surgery
Duke University Durham, North Carolina, USA
Stuart J. Knechtle, MD, FACS
William R. Kenan, Jr. Professor of Surgery Executive Director, Duke Transplant Center
Duke University School of Medicine Durham, North Carolina, USA
Simon R. Knight, MA, MB, MChir, FRCS
Senior Clinical Research Fellow Centre for Evidence in Transplantation Oxford Transplant Centre
Nuffield Department of Surgical Sciences University of Oxford Oxford, United Kingdom
Kate Kronish, MD
Assistant Professor Department of Anesthesia and Perioperative Care
University of California San Francisco San Francisco, California, USA
John C. LaMattina, MD
Associate Professor Surgery
University of Maryland School of Medicine Baltimore, Maryland, USA
Jennifer S. Lees, BA (Hons), MA (Cantab), MBChB, MRCP Clinical Research Fellow/Specialist Trainee in Nephrology
University of Glasgow/NHS Greater Glasgow and Clyde Glasgow, United Kingdom
Henri Leuvenink, PhD UMCG
Surgery
University Medical Center Groningen Grorolfningen, Netherlands
Jayme E. Locke, MD, MPH, FACS, FAST Associate Professor of Surgery Director University of Alabama at Birmingham Comprehensive Transplant Institute Birmingham, Alabama, USA
Michael R. Lucey, MB, BCh, MD Professor Medicine, Gastroenterology and Hepatology
University of Wisconsin School of Medicine and Public Health Madison, Wisconsin, USA
Matthew William Luedke, MD
Assistant Professor Department of Neurology Duke University; Department of Medicine, Division of Neurology Veterans Affairs Medical Center Durham, North Carolina, USA
Anne Louise Marano, BS/BA, MD
Assistant Professor Dermatology
Duke Univeristy
Durham, North Carolina, USA
Lorna P. Marson, MBBS, MD, FRCSEng, FRCSEd, FRCP(Ed)
Professor of Transplant Surgery Clinical Sciences (Surgery) University of Edinburgh Edinburgh, United Kingdom
Chantal Mathieu, MD, PhD Professor of Medicine
Faculty of Medicine Katholieke University of Leuven (KU Leuven); Head, Endocrinology University Hospitals Leuven; Laboratory of Clinical and Experimental Endocrinology
University of Leuven (KU Leuven) Leuven, Belgium
Madhav C. Menon, MBBS, MD, FACP Assistant Professor
Medicine Nephrology and Recanati-Miller Transplant Institute
Icahn School of Medicine at Mount Sinai New York City, New York, USA
Sir Peter J. Morris, MD, PhD, FRS, FRCS Emeritus Nuffield Professor of Surgery University of Oxford; Honorary Professor University of London; Nuffield Department of Surgical Sciences University of Oxford Oxford, United Kingdom
Elmi Muller, MBChB, PhD Professor Surgery
Groote Schuur Hospital University of Cape Town Cape Town, Western Cape, South Africa
Barbara Murphy, MD
Murray M. Rosenberg Professor of Medicine Chair of the Department of Medicine
Mount Sinai Health System
New York City, New York, USA
Sarah A. Myers, MD Professor Dermatology
Duke University Durham, North Carolina, USA
Brian J. Nankivell, MB, BS, MSc, PhD, MD, MRCP(UK), FRACP
Doctor, Renal Medicine
Westmead Hospital Westmead, New South Wales, Australia
Claus U. Niemann, MD Professor
Department of Anesthesia and Perioperative Care; Professor Department of Surgery
University of California San Francisco San Francisco, California, USA
John O’Callaghan, BSc, MBBS, DPhil
Specialty Registrar Transplantation Surgery
Oxford University Hospitals Oxford, United Kingdom
Philip John O’Connell, MD, PhD Director of Transplantation Renal Unit
University of Sydney at Westmead Hospital Westmead, New South Wales, Australia
Jon S. Odorico, MD Professor of Surgery Department of Surgery, Division of Transplantation University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA
Andrea Olmos, MD Assistant Professor Department of Anesthesia and Perioperative Care
University of California San Francisco San Francisco, California, USA
Gabriel Oniscu, MD, FRCS Consultant Transplant Surgeon Transplant Unit
Royal Infirmary of Edinburgh; Honorary Clinical Senior Lecturer Clinical Surgery University of Edinburgh Edinburgh, United Kingdom
Rachel E. Patzer, PhD, MPH Associate Professor Department of Surgery
Emory University School of Medicine; Rollins School of Public Health Department of Epidemiology Emory University Atlanta, Georgia, USA
Liset H.M. Pengel, PhD
Co-director
Peter Morris Centre for Evidence in Transplantation
Nuffield Department of Surgical Sciences
University of Oxford Oxford, United Kingdom
Andrew C. Peterson, MD, FACS Professor of Surgery
Duke University Medical Center; Urology Residency Program Director Duke University Durham, North Carolina, USA
Jacques Pirenne, MD, MSc, PhD Professor of Surgery Faculty of Medicine
University of Leuven (KU Leuven); Head
Abdominal Transplant Surgery University Hospitals Leuven; Director
Abdominal Transplant Surgery Laboratory Department of Microbiology and Immunology University of Leuven (KU Leuven) Leuven, Belgium
Rutger J. Ploeg, MD, PhD, FRCS
Professor of Transplant Biology and Consultant Surgeon Nuffield Department of Surgical Sciences University of Oxford Oxford, United Kingdom; Professor of Transplant Biology LUMC Transplant Centre
University of Leiden Leiden, Netherlands; Professor of Transplant Surgery Surgery
Medical Faculty
University of Groningen Groningen, Netherlands
Brenda Maria Rosales, BA, BMS (Honours), MPH
Sydney School of Public Health
The University of Sydney Sydney, New South Wales, Australia
Nasia Safdar, MD Professor Medicine, Infectious Diseases
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin, USA
Adnan Said, MD, MS
Associate Professor Medicine, Gastroenterology and Hepatology
University of Wisconsin School of Medicine and Public Health Madison, Wisconsin, USA
Caroline K. Saulino, PsyD
Medical Instructor Department of Psychiatry and Behavioral Sciences
Duke University Durham, North Carolina, USA
Carrie Schinstock, MD Doctor
Nephrology and Hypertension
Mayo Clinic
Rochester, Minnesota, USA
Paul M. Schroder, MD, PhD Research Fellow Department of Surgery
Duke University School of Medicine Durham, North Carolina, USA
Dorry L. Segev, MD, PhD Professor of Surgery and Epidemiology
Surgery
Johns Hopkins University; Associate Vice Chair Surgery
Johns Hopkins Hospital Baltimore, Maryland, USA
Ron Shapiro, MD Professor of Surgery, Surgical Director Kidney/Pancreas Transplantation Recanati/Miller Transplantation Institute
Icahn School of Medicine at Mount Sinai New York City, New York, USA
Daniel A. Shoskes, MD, MSc, FRCSC Professor of Urology Urology Cleveland Clinic Cleveland, Ohio, USA
Patrick J. Smith, PhD, MPH
Associate Professor Department of Psychiatry and Behavioral Sciences Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine
Department of Population Health Sciences, Center for Health Measurement
Duke University Medical Center Durham, North Carolina, USA
Ben Sprangers, MD, PhD, MBA, MPH
Associate Professor of Medicine Faculty of Medicine University of Leuven (KU Leuven); Department of Nephrology University Hospitals Leuven; Laboratory of Molecular Immunology (Rega Institute) Microbiology and Immunology University of Leuven (KU Leuven) Leuven, Belgium
Mark Stegall, MD
Transplant Center
Mayo Clinic
Rochester, Minnesota, USA
Ram M. Subramanian, MD
Associate Professor Medicine and Surgery
Emory University Atlanta, Georgia, USA
Craig J. Taylor, PhD, FRCPath
Consultant Clinical Scientist [Retired]
Histocompatibility and Immunogenetics (Tissue Typing) Laboratory
Cambridge University Hospitals Cambridge, Cambridgeshire, United Kingdom
John F. Thompson, MD
Professor of Melanoma and Surgical Oncology
The University of Sydney Melanoma Institute Australia; Professor of Surgery (Melanoma and Surgical Oncology)
Sydney Medical School
The University of Sydney Sydney, New South Wales, Australia
Vikram Wadhera, MD
Assistant Professor of Surgery
Recanati/Miller Transplantation Institute
Icahn School of Medicine at Mount Sinai New York City, New York, USA
Mark Waer, MD, PhD
Emeritus Professor of Medicine
Faculty of Medicine
University of Leuven (KU Leuven); Laboratory of Experimental Transplantation, Microbiology and Immunology University of Leuven (KU Leuven) Leuven, Belgium
Christopher J.E. Watson, MA, MD, BChir Professor of Transplantation Department of Surgery
University of Cambridge Cambridge, United Kingdom
Angela Claire Webster, MBBS, MM (Clin Epid), PhD Professor of Clinical Epidemiology School of Public Health University of Sydney Sydney, New South Wales, Australia; Senior Staff Specialist Centre for Transplant and Renal Research Westmead Hospital Westmead, New South Wales, Australia
Willem Weimar, MD, PhD Professor, Doctor Internal Medicine
Erasmus MC Rotterdam, Netherlands
Pamela D. Winterberg, MD
Assistant Professor
Pediatric Nephrology
Emory University School of Medicine; Children’s Healthcare of Atlanta Atlanta, Georgia, USA
Kathryn J. Wood, MD
Transplantation Research Immunology Group Nuffield Department of Surgical Sciences University of Oxford Oxford, United Kingdom
Diana A. Wu, MBChB Research Fellow Transplant Surgery University of Edinburgh Edinburgh, United Kingdom
CHAPTER OUTLINE
Kidney Transplantation: A History
DAVID HAMILTON
Early Experiments
Human Kidney Transplants
The Middle Years
Post World War II
Immunosuppression and the Modern Era
Chemical Immunosuppression
The modern period of transplantation began in the late 1950s, but two earlier periods of interest in clinical and experimental transplantation were the early 1950s and the first two decades of the 20th century. Hamilton1 provides a bibliography of the history of organ transplantation. Table 1.1 summarizes landmarks in kidney transplantation.
Early Experiments
Interest in transplantation developed in the early part of the 20th century because experimental and clinical surgical skills were rapidly advancing, and many of the pioneering surgeons took an interest in vascular surgical techniques as part of their broad familiarity with the advance of all aspects of surgery. Payr’s demonstration of the first workable, although cumbersome, stent method of vascular suturing led to widespread interest in organ transplantation in Europe. Many centers were involved, notably Vienna, Bucharest, and Lyon. The first successful experimental organ transplant was reported by Ullmann in 1902. Emerich Ullmann (1861–1937) (Fig. 1.1) had studied under Edward Albert before obtaining a position at the Vienna Medical School, which was then at its height. Ullmann’s article shows that he managed to autotransplant a dog kidney from its normal position to the vessels of the neck, which resulted in some urine flow. The animal was presented to a Vienna medical society on March 1, 1902, and caused considerable comment.2 At this time, Ullmann was chief surgeon to the Spital der Baumhertigen Schwestern, and his experimental work was done in the Vienna Physiology Institute under Hofrath Exner. Exner’s son Alfred had already tried such a transplant without success. In the same year, another Vienna physician, Alfred von Decastello, physician assistant at the Second Medical Clinic, carried out dog-to-dog kidney transplants at the Institute of Experimental Pathology.3
Ullmann and von Decastello had used Payr’s method, and later in 1902 Ullmann demonstrated a dog-to-goat kidney transplant that, to his surprise, passed a little urine
A Time of Optimism
Tissue Typing
The 1970s Plateau
Waiting for Xenografts
Conclusion
for a while. Neither Ullmann nor von Decastello continued with this work, although von Decastello was noted for his work on blood groups, and Ullmann published extensively on bowel and biliary surgery.
In Lyon, the department headed by Mathieu Jaboulay (1860–1913) had a major influence (Fig. 1.2). In his research laboratories, his assistants Carrel, Briau, and Villard worked on improved methods of vascular suturing, leading to Carrel’s famous article credited with establishing the modern method of suturing.4 Carrel left to work in the United States, and in the next 10 years he published extensively on organ grafting, successfully carrying out autografts of kidneys in cats and dogs and, showing that allografts, contrary to accepted opinion, eventually failed after functioning briefly, established the existence of “rejection” as it was later termed. He made attempts at tissue matching and demonstrated cold-preservation of tissues. He was awarded a Nobel Prize for this work in 1912.5
Human Kidney Transplants
Jaboulay, Carrel’s teacher, had carried out the first recorded human kidney transplant in 1906,6 although Ullmann later claimed an earlier attempt in 1902.7 Jaboulay was later to be better known for his work on thyroid and urologic surgery, but, doubtless encouraged by the success of Carrel and others in his laboratory, he carried out two xenograft kidney transplants using a pig and goat as donors, transplanting the organ to the arm or thigh of patients with chronic renal failure. Each kidney worked for only 1 hour. This choice of an animal donor was acceptable at that time in view of the many claims in the surgical literature for success with xenograft skin, cornea, or bone.
More is known of the second and third attempts at human kidney transplantation. Ernst Unger (1875–1938) (Fig. 1.3) had a thorough training in experimental work and set up his own clinic in 1905 in Berlin, being joined there by distinguished colleagues. He continued with experimental work and by 1909 reported successful
TABLE 1.1 Landmarks in Kidney Transplantation
1902 First successful experimental kidney transplant2
1906 First human kidney transplant—xenograft6
1933 First human kidney transplant—allograft54
1950 Revival of experimental kidney transplantation4,16,57
1950–1953 Human kidney allografts without immunosuppression, in Paris18,19,56,59 and Boston21
1953 First use of live related donor, Paris20
1954 First transplant between identical twins, Boston22
1958 First description of leukocyte antigen MAC62
1959–1962 Radiation used for immunosuppression, in Boston24 and Paris25,56
1960 Effectiveness of 6-mercaptopurine (6-MP) in dog kidney transplants29,42
1960 Prolonged graft survival in patient given 6-MP after irradiation34
1962 First use of tissue matching to select a donor and recipient44,47,49,56
1966 Recognition that positive crossmatching leads to hyperacute rejection29,50,56
1967 Creation of Eurotransplant46
1967 Development of kidney preservation
1973 Description of the transfusion effect57
1978 First clinical use of cyclosporine55
1978 Application of matching for HLA-DR in renal transplantation29
1987 First of new wave of immunosuppressive agents appears (tacrolimus)
1997 Transgenic pigs strategy63
2010 Laparoscopic kidney insertion64
transplantation of the kidneys en masse from a fox terrier to a boxer dog. The urine output continued for 14 days, and the animal was presented to two medical societies. By 1910, Unger had performed more than 100 experimental kidney transplants. On December 10, 1909, Unger attempted a transplant using a stillborn child’s kidney grafted to a baboon. No urine was produced. The animal died shortly after the operation, but postmortem examination showed that the vascular anastomosis had been successful. This success and the new knowledge that monkeys and humans were serologically similar led Unger to attempt, later in the same month, a monkey-to-human transplant.8 The patient was a young girl dying of renal
Fig. 1.2 Mathieu Jaboulay (1860–1913) and his surgical team at Lyon in 1903. Until his death in a rail accident, Jaboulay made numerous surgical contributions and encouraged Alexis Carrel’s work on vascular anastomosis. In 1906 Jaboulay reported the first attempt at human kidney transplantation.
Fig. 1.3 A contemporary cartoon of Ernst Unger (1875–1938) at work at the Rudolf Virchow Hospital, Berlin. (Courtesy the Rudolf Virchow Hospital.)
Fig. 1.1 Emerich Ullmann (1861–1937) carried out the first experimental kidney transplants in dogs in 1902. (Courtesy the Vienna University, Institute for the History of Medicine.)
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serrūdia(LaC.)
s'ētra(H-M.)
sētta(H-M.)
Daucus Carota L. f. radice parva
Thymus serpyllum L.
Ornithogalum umbellatum L.
setūn(H-M.) Olea europaea L.
ssāle-lensār(H-M.)
ess-ssāq-alekhhal(B.)
ss'āqet-el-qott.tt(B.)
ssbulat-el-far(B.)
ssbūqa(B.)
ssēf-el-ghrāb(B. H-M.)
sseïsseī(B.)
ssekérschu(B.)
ssekkūm,ssukkōm(HM.)
sselq(B.)
Verbascum sinuatum L.
Adianthum CapillusVeneris L.
Daucus maximus Desf.
Phalaris caerulescens
Desf.
Sambucus nigra L.
Gladiolus segetum L.
Salix pedicellata Desf.
Calystegia sepium R.Br. (= Convolvulus)
Asparagus albus L.
Beta vulgaris L.
ssemlīl,ssemlēl(B. H-M.)
Salix pedicellata Desf.
ssennaría(LaC.) Daucus Carota L.
sseq-ett-ttēr(LaC.) Neslia paniculata Desf.
sseruēl,sseruīl(B.)
Cupressus sempervirens L.
ssibūtss(H-M.) Andropogon hirtus L.
ssilla(H-M.) Hedysarum coronarium L.
ssitssémber(B.)
sskerga(B.)
sskerschu(B.)
Mentha piperita L.
Calystegia sepium R.Br. (= Convolvulus)
Smilax aspera L.
ssmēter(B.) Pteris aquilina L.
ssolttān-el-ghaba(B.)
ssrīss(B.)
Smyrnium olusatrum L.
Campanula Erinus L.
ssrīss(B.) Anagallis caerulea L.
ssuāk-raijān(H-M.) Scorpiurus muricatus L.
schā'ar-el-fār(B.)
Stipa tortilis Desf.
scha'r-el-erneb(B.)
scha'āret-el-ma'īs(B.)
schegeret-Meriam(B.)
schenān,schnān(B.)
schendqūra(B.)
schenef(B.)
scherraíeq(H-M.)
schina,schna(B.)
esch-schōk-el-asreq(B.)
schōk-el-bēdda(H-M.)
schōk-ed-dhab'(H-M.)
schōk-el-hhamir(B.)
schōk-el-hhánesch(HM.)
schōk-el-hhomār(B.)
schōk-es-serqa(B.)
Lagurus ovatus L.
Umbellifer. sp.
Artemisia arborescens L.
Melilotus indica Lam.
Ajuga Iva L.
Erodium chium W.
Iris Sisyrynchium L.
Citrus Aurantium L.
Galactites tomentosa
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Cirsium lanceolatum L.
Eryngium triquetrum
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Galactites tomentosa
Mch.
Galactites tomentosa
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Echinops spinosus L.
Galactites tomentosa
Mch.
tafrīra,tfēfra(B.)
tahhuirāt(B.)
teb-er-rajān(B. H-M.)
tefifhha(B.)
tefra(B. H-M.)
terirásch(B.)
terttūq(B.)
téssekra(H-M.)
tessulāt(B.)
tibíua(B.)
!tiféf(B.)
tilfēf(H-M.)
tifitáss(B.)
tirlelt(B.)
tsilfāt(H-M.)
tuffélt(H-M.)
tūt(B.)
!Acanthus mollis L.
Papaver Rhoeas L.
Ononis alba Forsk.
Matricaria chamomilla L.
Cardopatium corymbosum Sp.
Rhaponticum acaule D.C.
Centaurea Seridis L.
Silene inflata L.
Genista numidica Sp.
Echinops spinosus L.
Hedysarum coronarium L.
Ficaria calthifolia Reich.
Sonchus oleraceus L.
Linum angustifolium L.
Cyperus longus L.
Sonchus arvensis L.
Verbascum sinuatum L.
Morus alba L.
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thatba(B.)
thinūg(H-M.)
Crataegus oxyacantha L.
Genista numidica Sp.
Nigella arvensis L.
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tssabūn-el-'aráiss(B.)
tssaftssāf(B. LaC.)
tssala-landhār(H-M.)
tssalahh-el-enttār(B.)
tsserāt-el-ardd(B.)
tssettbat(B.)
Inula viscosa Ait.
Populus alba L.
Populus nigra L.
Verbascum sinuatum L.
Verbascum sinuatum L.
Urospermum
Dalechampii Desf.
Genista sp.
ttafss(B.)
ttreilāl,ttreilān(B.)
Daucus muricatus L.
Chrysanthemum Clausonis Pom.
uard-el-chla'(B.)
uard-el-ghaba(B.)
uard-er-réqa(B.)
'ūd-el-áhhmar,'ūd-elhhomr(B.)
Gladiolus segetum L.
Gladiolus segetum L.
Gladiolus segetum L.
Alnus glutinosa L.
'ūd-el-chēr(LaC.) Ilex Aquifolium L.
'udhēn-dhīb(B.)
'udhēn-el-hhalūf(B.)
um-ess-ssuālef(B.)
Arum italicum L.
Arum italicum L.
Salix babylonica L.
[30]d.i. „die kleine blaue“.
[31]Kabylisch: „asénsu“.
B. LATEINISCH-ARABISCH GEORDNETER TEIL
!Acanthus mollis L. tafrīra,tfēfra(B.)
Adianthum CapillusVeneris L. ess-ssāq-alekhhal(B.)
Hedysarum coronarium L. ⎰ ⎱ ssilla(H-M.) tessulāt(B.)
Helminthia echioides L. hharscha(B.)
Hypericum perforatum L. hhaschīschet-el-hhasaïs (B.)
Hyoscyamus albus L. bu-mergūf(B.)
Jasminum officinale L. ⎰ ⎱ full(B.)
jassmīn(B.)
Ilex Aquifolium L. ⎰ ⎱ qettém(LaC.)
'ūd-el-chēr(LaC.)
Inula crithmoides L. memēje(B.)
bugranān(H-M.)
meqremān,meqramēn (B.)
Inula viscosa Ait.
merssīta(LaC.)
tssabūn-el-'aráiss(B.)
Iris Pseudacorus L. borbēt(LaC.)
Iris Sisyrynchium L. scherraíeq(H-M.) K
Koniga maritima R.Br. qornúnasch-el-gebel(B.)
Lagurus ovatus L. scha'r-el-erneb(B.)
Lathyrus Ochrus L. girfēla(H-M.)
Lavandula Stoechas L. ⎰ ⎱ chelchāla(B.) hhalhhāla(B.)
Linum angustifolium L. tifitáss(B.)
Lolium temulentum L. ⎰ ⎱
qellēb,qellāb(B. LaC.)
sakkūm(LaC.)
Lonicera implexa L. mahbūla(LaC.)
nuuār-ssuēua(B.)
Lupinus luteus L.
rbīb-ed-driass(B.)
Malva parviflora L. chobbēs(H-M.)
Malva sylvestris L. chobeīsa(B.)
ddemrān,ddomrān(B.)
Marrubium vulgare L.
meql-etss-tssēf(B. H-M.)
merriūt(H-M.)
Matricaria chamomilla L. tefifhha(B.)
Medicago Murex L. ifiss-el-beqer(B.)
Melilotus indica Lam. schenān,schnān(B.)
Melissa officinalis L. hhaschīschet-en-nhhāl (B.)
Mentha aquatica L. flēju,flīju(B.)
Mentha piperita L. ssitssémber(B.)
Micromeria nervosa Bth. sá'etra(B.)
Morus alba L. tūt(B.)
Muscari comosum btssal-dhīb(B.)
less.ssāka(B.)
Musci sp. omnes
letssāqa(B.)
Myrtus communis L. rihhān(B.)
N
Narcissus Tazetta L. nuuār-es-suāra(B.)
Nasturtium officinale L. qernūnesch(B.)
defla(B.)
Nerium Oleander L.
dífle(H-M.)
Neslia paniculata Desf. sseq-ett-ttēr(LaC.)
Nigella arvensis L. thinūg(H-M.)
Nonea nigricans Desf. nussāhssa(H-M.)
Olea europaea L. f. oleaster sebūg(B.)
Olea europaea L. setūn(H-M.)
Ononis alba Forsk. teb-er-rajān(B. H-M.)
Onopordum macracanthum Shousb. qernīna(B.)
Opuntia ficus indica L. el-hendi(H-M.)
Origanum Majorana L. mardaqūsch(B.)
bohorr-el-berri(B.)
Ornithogalum arabicum L.
sētta(H-M.)
Osyris alba L.
bu-tssāla'(B.)
nathāss(B. H-M.)
sās(B.)
Papaver Rhoeas L.
bu-qra'ūn(B.),
buqraōn(H-M.)
tahhuirāt(B.)
Papaver somniferum L. chaschchásch, cheschchāsch(B. LaC.)
Parietaria officinalis L. hhaschīschet-er-ri'(B.)
Paronychia argentea Lam. kiftsē(H-M.)
Phalaris caerulescens
Desf.
berāqa(B.)
ssbulat-el-far(B.)
Phagnalon rupestre D.C. g'aïda(B.)
Phlomis floccosa L. kmémta(B.)
Phragmites communis L. qtssāb,qtssōb(B.)
Phytolacca dioica L. a'aqqarr(B.)
Pistacia Lentiscus L. ⎰ ⎱ ddarū,dderū,ddrū(LaC.)
dsrū(B. LaC.)
Plantago coronopus L. ⎰
gnība(B.)
maqramān(B.)
Plantago Lagopus L. nuuār-el-aqrab(H-M.)
Poa trivialis L. qellēb,qellāb(B. LaC.)
Populus alba L.
Populus nigra L.
tssaftssāf(B. LaC.)
Prasium majus L. rihhān-el-ghrīb(B.)
Prunus domestica L. a'in-baqar(H-M.)
Prunus insititia L. sa'arūr(B.)
Pteris aquilina L.
ferssīk(LaC.) ssmēter(B.)
Pulicaria viscosa L. bu-gremēn(H-M.)
Pyrus communis L. lansāsch(el-hansāsch) (H-M.)
Quercus suber L.
fernān(B.)
ballūtt-qescherīt(LaC.)
Quercus Mirbeckii Duv. sēn(B.) R
Ranunculus acris L. muttār,muttēr(B.)
Ranunculus trachycarpus F. M. keff-el-gerāna(LaC.)
b'atssūtss-el-charūf(B.)
Reseda alba L.
dhēl-el-chrūf(B. H-M.)
dhēl-en-na'aga(B.)
Rhamnus alaternus L. melīliss,mlīless(B.)
Rhaponticum acaule D.C. tefra(B. H-M.)
Rosa canina L. bu-tssūfa(H-M.)
Rosmarinus officinalis L. klēl,kelīl(B.)
Rubus discolor Weihe. 'allēq(B. H-M.)
Rumex bucephalophorus L. hhaschīschet-el-qartssa (B.)
Rumex dentatus L. hhommēd(H-M.)
Ruta chalepensis L. figēl(B. H-M.)
SSalix babylonica L.
Salix pedicellata Desf. ⎰ ⎱
um-ess-ssuālef(B.)
sseïsseī(B.)
ssemlīl,ssemlēl(B. H-M.)
Salvia argentea L. frēsch-en-ndā(B.)
Salvia bicolor Desf. 'aschba-kull-alblía'(B.)
Sambucus nigra L. ssbūqa(B.)
Scabiosa maritima L. chejattāt-el-geráhh, cheijátt-el-geráhh(B.)
Scandix pecten-veneris L. meschtta(B.)
Scilla peruviana L. butssēla(H-M.)
Scolymus hispanicus L. ⎰ ⎱ gernīss(LaC.) sernīs(B. LaC.)
Scolymus maculatus L. buqq(H-M.)
Scolymus hispanicus L. ⎱ ⎰ qornēna(H-M.)
!Scolymus maculatus L.
Scorpiurus muricatus L. ssuāk-raijān(H-M.)
Secale cereale L. barrāka(LaC. B.)
Sedum caeruleum Vahl. betssūl-elqétt.tta(H-M.)
Serapias cordigera L. muhháget(LaC.)
Silene gallica L. hhaschīschet-edh-dhubān (B.)
Silene inflata L. terirásch(B.)
Silybum Marianum Gaert. qorēna(H-M.)
Sinapis arvensis L. libssān(B. H-M.)
Sisymbrium officinale L. belgh-erniss(B.)
Smilax aspera L.
Smyrnium olusatrum L.
Solanum nigrum L.
'amb-edh-dhīb 'aneb-edh-dhīb(H-M.) sskerschu(B.)
geda'(B.)
gerrēd(H-M.)
ichtssetss(B.)
ssolttān-el-ghaba(B.)
'éneb-edh-dhīb(B.)
ramrām(LaC.)
Sonchus arvensis L. tsilfāt(H-M.)
Sonchus oleraceus L. ⎰ ⎱ !tiféf(B.)
tilfēf(H-M.)
Sparganium ramosum L. chebūq(LaC.)
Stipa tortilis Desf. schā'ar-el-fār(B.)
TTamus communis L. ⎰ ⎱
bel-memūn,
ben-memūn(B.)
Teucrium scordioides Schr. magl-etss-tssēf(H-M.)
!Thapsia garganica L. drīass,drīess(B. Kabyl. HM.)
Thymelaea hirsuta L. metenēn(H-M.)
Thymus serpyllum L. ⎰
sa'āter(B.)
s'ētra(H-M.)
Trapa natans L. bu-qornēn,bu-qornūn (LaC.)
Trifolium repens L. bu-schuēscha,buschuīscha(LaC. H-M.)
Trifolium Jaminianum B. lifla(H-M.)
Trixago apula St. 'ánfes(B.)
Umbellifer. sp. radix belgh-erniss(B.)
Umbellifer. sp. mtssātssa(B.)
Umbellifer. sp. scha'āret-el-ma'īs(B.)
Umbilicus horizontalis Guss.
Urginea maritima Bak.
Urospermum Dalechampii Desf.
mustāssa(H-M.)
'ántssal(B. H-M.)
btssel-edh-dhīb(B.)
faraūn(B.)
!fr'aūn(B.)
tsserāt-el-ardd(B.)
Urtica pilulifera L. hhorrēq(B. H-M.)
VVicia lutea L.
Viola odorata L.
Verbascum sinuatum L.
gelbanat-el-hhanesch, gilbān-el-hhanesch(B.)
belssfeng(B.)
ssāle-lensār(H-M.)
tuffélt(H-M.)
tssalahh-el-enttār(B.)
tssala-landhār(H-M.)
Ziziphus spina-Christi L. 'enēb(B.)
[32]d.i. „die kleine blaue“.
[33]Kabylisch: „asénsu“.
ABTEILUNG VI
IN AEGYPTEN UND ALGERIEN GEBRÄUCHLICHE
NOMENKLATUR DER DATELPALME
(PHOENIX DACTYLIFERA L.)
ABKÜRZUNGEN
zur Bezeichnung der Örtlichkeiten, an denen die arabischen Ausdrücke aufgezeichnet wurden. Wo keine Örtlichkeit angegeben, gilt der Ausdruck für das ganze Land.
